Effects of age on pharmacokinetics of central nervous system drugs were studied. Biodisposition of haloperidol and phenobarbital was examined in male, Fischer-344 rats of four different age groups, 3-4, 11-12, 23-24, and 32-34 months. Drugs were administered intraperitoneally, either as a bolus or continuously from implanted osmotic minimpumps. Plasma and brain concentrations were determined for these drugs, after extraction, by gas chromatographic analysis with a nitrogen selective detector. Similar age-related alterations in pharmacokinetic profiles of these two drugs were observed although the drugs have different pharmacotherapeutic, physicochemical and pharmacokinetic properties. Significantly higher plasma and brain concentrations of both drugs were found in the older as compared to younger rats, due to a decreased apparent plasma clearance following a bolus and during continuous administration. Plasma concentrations were not directly predictive of brain concentrations, because the brain/plasma concentration ratio of the drugs did not remain constant during aging. These studies are a first step to understanding of altered clinical responsivity to drugs in the elderly.